Next Article in Journal
PEG–Ursolic Acid Conjugate: Synthesis and In Vitro Release Studies
Previous Article in Journal
Role of an Ethanolic Extract of Crotalaria juncea L. on High-Fat Diet-Induced Hypercholesterolemia
Article Menu

Article Versions

Export Article

Open AccessArticle
Sci. Pharm. 2013, 81(2), 359-392; doi:10.3797/scipharm.1211-08

Synthesis and Anticancer Activity of 2-(Alkyl-, Alkaryl-, Aryl-, Hetaryl-)-[1,2,4]triazolo[1,5-c]quinazolines

1
Organic and Bioorganic Chemistry Department, Zaporizhzhya State Medical University, Mayakovsky Ave. 26, 69035, Zaporizhzhya, Ukraine
2
Enamine Ltd., Oleksandra Matrosova 23, Kyiv, 01103, Ukraine
*
Author to whom correspondence should be addressed.
Received: 13 November 2012 / Accepted: 23 December 2012 / Published: 23 December 2012
Download PDF [396 KB, uploaded 27 September 2016]

Abstract

The combinatorial library of novel potential anticancer agents, namely, 2-(аlkyl-, alkaryl-, aryl-, hetaryl-)[1,2,4]triazolo[1,5-c]quinazolines, was synthesized by the heterocyclization of the аlkyl-, alkaryl-, aryl-, hetarylcarboxylic acid (3Н-quinazoline-4-ylidene)hydrazides by oxidative heterocyclization of the 4-(arylidenehydrazino)quinazolines using bromine, and by the heterocyclization of N-(2-cyanophenyl)formimidic acid ethyl ester. The optimal method for synthesis of the s-triazolo[1,5-c]quinazolines appeared to be cyclocondensation of the corresponding carboxylic acid (3H-quinazoline-4-ylidene)hydrazides. The compounds’ structures were established by 1H, 13C NMR, LC- and EI-MS analysis. The in vitro screening of anticancer activity determined the most active compound to be 3,4,5-trimethoxy-N'-[quinazolin-4(3H)-ylidene]benzohydrazide (3.20) in micromolar concentrations with the GI50 level (MG_MID, GI50 is 2.29). Thus, the cancer cell lines whose growth is greatly inhibited by compound 3.20 are: non-small cell lung cancer (NCI-H522, GI50=0.34), CNS (SF-295, GI50=0.95), ovarian (OVCAR-3, GI50=0.33), prostate (PC-3, GI50=0.56), and breast cancer (MCF7, GI50=0.52), leukemia (K-562, GI50=0.41; SR, GI50=0.29), and melanoma (MDA-MB-435, GI50=0.31; SK-MEL-5, GI50=0.74; UACC-62, GI50=0.32). SAR-analysis is also discussed.
Keywords: [1,2,4]Triazolo[1,5-c]quinazolines; Anticancer activity; Carboxylic acid (3Н-quinazoline-4-ylidene)hydrazides; N-(R-Benzylidene)-N'-(3Н-quinazoline-4-ylidene)hydrazines; 2-Alkyl (alkaryl-, aryl-, hetaryl-)[1,2,4]triazolo[1,5-c]quinazolines [1,2,4]Triazolo[1,5-c]quinazolines; Anticancer activity; Carboxylic acid (3Н-quinazoline-4-ylidene)hydrazides; N-(R-Benzylidene)-N'-(3Н-quinazoline-4-ylidene)hydrazines; 2-Alkyl (alkaryl-, aryl-, hetaryl-)[1,2,4]triazolo[1,5-c]quinazolines
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

KOVALENKO, S.I.; ANTYPENKO, L.M.; BILYI, A.K.; KHOLODNYAK, S.V.; KARPENKO, O.V.; ANTYPENKO, O.M.; MYKHAYLOVA, N.S.; LOS, T.I.; KОLОMОЕTS, O.S. Synthesis and Anticancer Activity of 2-(Alkyl-, Alkaryl-, Aryl-, Hetaryl-)-[1,2,4]triazolo[1,5-c]quinazolines. Sci. Pharm. 2013, 81, 359-392.

Show more citation formats Show less citations formats

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Sci. Pharm. EISSN 2218-0532 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top